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Synthesizing method of nafcillin acid

A technology of nafcillin acid and synthesis method, which is applied in the field of semi-synthetic antibiotic nafcillin sodium, can solve the problems of great influence on the yield of the target product, cumbersome and complicated operation process, and physical hazards of operators, so as to reduce human harm and environmental pollution, avoid repeated phase separation, and reduce the effect of labor

Active Publication Date: 2013-11-06
朗致集团江西医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The biggest disadvantage of using organic solvents is serious environmental pollution, great harm to operators, and high production costs. In addition, the condensation reaction in organic solvents requires acidification, phase separation, alkalization, and phase separation in the later stage to obtain purity. Higher nafcillin sodium aqueous solution, the operation process is loaded down with trivial details and complexity, and labor load is big, and has great influence on the yield of target product

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Add 45kg of 6-APA to the reaction tank with 90L of purified water, cool down to 0°C, add 225L of 3.7% sodium hydroxide solution in a trickle, after 6-APA is dissolved and clarified, add 1-chloroformyl-2 in 10min - 45kg of ethoxynaphthalene solids, during the addition of 1-chloroformyl-2-ethoxynaphthalene solids, use 3.7% sodium hydroxide solution to control the pH value of the reaction solution at 7.0, and keep the reaction at 20°C for 15 minutes after the addition is complete . Add 2kg of activated carbon, stir for 20min, filter the activated carbon, add 78kg of butyl acetate to the filtrate, cool down to 0-10°C, acidify with 3% dilute sulfuric acid to pH=1.5-2.0, precipitate crystals, continue to stir for 1h, shake off, filter with purified water Wash the crystals until the pH of the washing solution is 4.0, dry the washed filter cake, put it on a plate, put it in a vacuum drying oven at 45-55°C, and dry it to a moisture content of 2.4% to obtain 77.8 kg of nafcillin ...

Embodiment 2

[0023] Add 45kg of 6-APA to the reaction tank with 180L of purified water, cool down to 5°C, add 220L of 8% sodium bicarbonate solution in a trickle, after 6-APA is dissolved and clarified, add 1-chloroformyl-2 in batches within 13 minutes -Ethoxynaphthalene solid 47.3kg, during the addition of 1-chloroformyl-2-ethoxynaphthalene solid, use 8% sodium bicarbonate solution to control the pH value of the reaction solution at 7.2, after the addition is completed, keep the reaction at 18°C ​​for 20min . Add 2 kg of activated carbon, stir for 20 minutes, filter the activated carbon, add 68 kg of n-hexane to the filtrate, cool down to 0-10°C, acidify with 5% dilute hydrochloric acid to pH 1.5-2.0, precipitate crystals, continue to stir for 1 hour, and filter with purified water Wash the crystals until the pH of the washing solution is 4.0, dry the washed filter cake, put it into a tray, put it in a vacuum drying oven at 45-55°C, and dry it to a moisture content of 2.0% to obtain 78.6 ...

Embodiment 3

[0025] Add 45kg of 6-APA to the reaction tank with 220L of purified water, cool down to 3°C, add 220L of 5% sodium carbonate solution in a trickle, after 6-APA is dissolved and clarified, add 1-chloroformyl-2- 49.5 kg of ethoxynaphthalene solids, during the addition of 1-chloroformyl-2-ethoxynaphthalene solids, use 5% sodium carbonate solution to control the pH value of the reaction solution at 6.8, and keep the reaction at 15°C for 30 minutes after the addition is complete. Add 2 kg of activated carbon, stir for 20 minutes, filter the activated carbon, add 73 kg of ethyl acetate to the filtrate, cool down to 0-10 ° C, acidify with 2% dilute phosphoric acid to pH 1.5-2.0, precipitate crystals, continue stirring for 1 hour, shake off the filter, and purify Wash the crystals with water until the pH of the washing solution is 4.0, dry the washed filter cake, put it on a plate, put it in a vacuum drying oven at 45-55°C, and dry it to a moisture content of 1.8%, to obtain 78.3 kg of...

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Abstract

The invention discloses a synthesizing method of nafcillin acid. According to the method, 6-aminopenicillanic acid is suspended in purified water, and is dissolved by inorganic base. 1-chloroformyl-2-naphthyl ethoxyl solid is added to the solution, and the mixture is subject to a reaction with a pH value maintained at 6.8 to 7.2, such that a condensate is obtained. The condensate is decolored, extracted, and acidified, such that crystals are precipitated. The material is dried, such that nafcillin acid is obtained. Compared to prior arts, according to the invention, organic solvents are substituted by purified water, an acid collection agent triethylamine is substituted by inorganic base, the uses of organic solvent and organic base are eliminated, such that cost is reduced, and harm to human and ham to the environment are maximally reduced. The method is suitable to be applied in industrialized productions.

Description

technical field [0001] The invention relates to a semi-synthetic antibiotic nafcillin sodium, in particular to a method for synthesizing an intermediate nafcillin acid used to produce nafcillin sodium. Background technique [0002] Nafcillin sodium is also known as ethoxynaphthylin penicillin, new penicillin Ⅲ, chemical name (2S,5R)-3,3-dimethyl-6-(2-ethoxy-1-naphthyl)-7-oxidation- 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid sodium salt monohydrate, molecular formula C 21 h 21 o 5 N 2 SNa·H 2 O, molecular weight 454.49, trade name Unipen, first developed by Wyeth Company in the United States, acid-resistant and penicillin-resistant enzyme, can be taken orally and injected, with exact curative effect and convenient use, suitable for penicillin-resistant Staphylococcus infection and other penicillin-sensitive bacterial infections , Such as: sepsis, endocarditis, empyema, liver abscess, pneumonia, osteomyelitis, etc. [0003] Nafcillin acid is an important interme...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D499/74C07D499/12
Inventor 陆晨阳刘秀兰李忠华任青花刘彦伟
Owner 朗致集团江西医药有限公司